Clinical Outcomes of Trimethoprim/Sulfamethoxazole in Critically Ill Patients with Stenotrophomonas maltophilia Bacteremia and Pneumonia Utilizing Renal Replacement Therapies.

Background: The clinical outcomes of usual doses of Trimethoprim-sulfamethoxazole (TMP/SMZ) for treating S. maltophilia in critically ill patients on renal replacement therapies (RRT) have not been established. We sought to assess the clinical outcomes of TMP/SMZ in patients with sepsis utilizing RRT. Methods: A retrospective study was performed on all critically ill adult patients with S. maltophilia infections who received RRT between May 2015 and January 2022. The primary endpoint was clinical cure while the secondary endpoints were microbiologic cure, 30-day infection recurrence, and mortality. Results: Forty-five subjects met the inclusion criteria. The median age was 70.0 [interquartile range (IQR): 63.5-77] years, 57.8% were males, and the median body mass index was 25.7 [IQR: 22-30.2] kg/m2. Clinical success and failure were reported in 18 (40%) and 27 (60%) cases, respectively. There was no significant difference between the 30-day reinfection rates of both groups; however, mortality was significantly higher in the clinical failure group, involving 12 patients (44.4%), versus none in the clinical success group (p = 0.001). The median daily dose of TMP/SMZ upon continuous veno-venous hemofiltration was 1064 [IQR: 776-1380] mg in the clinical cure group vs. 768 [IQR:540-1200] mg in the clinical failure group (p = 0.035). Meanwhile, the median dose for those who received intermittent hemodialysis was 500 [IQR: 320-928] mg in the clinical success group compared to 640 [IQR: 360-1005] mg in the clinical failure group (p = 0.372). A total of 55% experienced thrombocytopenia, 42% hyperkalemia, and 2.2% neutropenia. The multivariable logistic regression analysis showed that the total daily dose at therapy initiation was the only independent factor associated with clinical success after adjusting for different variables including the body mass index [Odds ratio 1.004; 95% confidence interval: (1-1.007), p = 0.044]. Conclusions: Although the S. maltophilia isolates were reported as susceptible, TMP/SMZ with conventional doses to treat bacteremia and pneumonia in critically ill patients utilizing RRT was associated with high rates of clinical and microbiologic failure as well as with mortality. Larger outcomes and pharmacokinetics studies are needed to confirm our findings.

Sustaining Life versus Altering Life-Saving Drugs: Insights to Explain the Paradoxical Effect of Extracorporeal Membrane Oxygenation on Drugs.

There has been a substantial increase in the use of extracorporeal membrane oxygenation (ECMO) support in critically ill adults. Understanding the complex changes that could affect drugs' pharmacokinetics (PK) and pharmacodynamics (PD) is of suitable need. Therefore, critically ill patients on ECMO represent a challenging clinical situation to manage pharmacotherapy. Thus, clinicians' ability to predict PK and PD alterations within this complex clinical context is fundamental to ensure further optimal and, sometimes, individualized therapeutic plans that balance clinical outcomes with the minimum drug adverse events. Although ECMO remains an irreplaceable extracorporeal technology, and despite the resurgence in its use for respiratory and cardiac failures, especially in the era of the COVID-19 pandemic, scarce data exist on both its effect on the most commonly used drugs and their relative management to achieve the best therapeutic outcomes. The goal of this review is to provide key information about some evidence-based PK alterations of the drugs used in an ECMO setting and their monitoring.